Bone metastases and use of bone protective agents (BPA) for metastatic renal cell carcinoma (mRCC): A contemporary national real-world analysis.

490 Background: Bone Metastases (BM) occur in approximately 30% of mRCC patients (pts) with evidence suggesting that they portend a worse prognosis. Systemic therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI) are felt to be active in these pts, with radiation therapy (RT) often employed for BM-directed treatment. The evidence for and use of BPAs, such as bisphosphonates and denosumab, is limited in the current ICI era. We investigated the outcomes of mRCC pts with BM and use of BPA in a contemporary real-world cohort. Methods: We analyzed data collected from the prospectively maintained, multi-institutional Canadian Kidney Cancer Information System (CKCis). Patients with clear cell mRCC treated between January 2011-June 2023 were included. Outcomes were compared between BM+ and BM- pts using Cox proportional hazards models. Kaplan-Meier estimates were used to assess time to treatment failure (TTF) and overall survival (OS) adjusted by IMDC criteria. Results: Of 2,307 patients with clear cell mRCC, 893 (39%) had BM+, of whom 691 (77%) underwent RT, and 139 (16%) received a BPA. Median follow-up was longer for BM- patients (34.6 vs 29.1 mos). Significant differences were noted in Karnofsky performance status (> 80%: 84% vs 78%), IMDC risk group (intermediate/poor: 76% versus 82%) use of RT (35% vs 78%), and use of BPAs (2% vs 16%) between BM- vs BM+ pts (all p < 0.05). In our cohort, first-line treatment in BM+ pts was monotherapy TKI (67%), doublet ICI (20%), and combination TKI+ICI (13%). Median TTF was similar in BM- vs BM+ pts: 9.6 vs 8.6 mos (HR 0.92; 95% CI 0.91-1.02). However, median OS was higher in BM- vs BM+ pts: 57.6 vs 35.8 mos (HR 0.67; 0.58-0.76; p<0.0001); this was consistent irrespective of type of systemic therapy. In BM+ pts, those who did not receive BPAs had a lower TTF (7.9 vs 13.4 mos) and OS (34.0 vs 46.0 mos); however, these were not statistically different when adjusted by IMDC criteria (TTF HR 1.2; 0.95-1.51 and OS HR 1.12; 0.85-1.46). There was no significant difference in TTF (HR 0.89; 0.72-1.10) or OS (HR 0.94; 0.73-1.22) in BM+ pts selected to receive RT. Conclusions: BM remain a poor prognostic factor in mRCC in this contemporary cohort of patients. While BPA use was limited, we observed no improvement in TTF or OS in BM+ pts with their use. These data warrant further investigation of BPA in mRCC including assessment of SREs and potential complications.